Significance of heparin-binding growth factor expression on cells of solid pediatric tumors

Abstract

Background: The heparin-binding growth factors pleiotrophin (PTN), midkine (MK), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) stimulate tumor cell proliferation and angiogenesis. In this study the authors wanted to know if these growth factors are expressed by cell lines and tumor tissue of solid pediatric tumors, growth factor expression is influenced by proinflammatory cytokines, and local growth factor concentration has an influence on experimental tumor growth. Methods: Growth factor mRNA expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and protein secretion by enzyme-linked immunosorbent assay (ELISA). Neuroblastoma cells were suspended in solutions containing different growth factor concentrations before injection into the nude mice, which were given pentosan polysulfate (PPS) for antagonism. Results: The analyzed growth factors were expressed by most cells of solid malignant pediatric tumors. Their expression was not influenced by proinflammatory cytokines. The inhibition of tumor growth by PPS in the nude mouse model was dependent on the local growth factor concentration. High concentration excluded significant tumor suppression. Conclusions: Because of the redundancy of growth factor expression and the abolishment of PPS efficacy by a high local growth factor concentration, the authors conclude that overall targeting of growth factors is a promising approach to cancer therapy in childhood.